Several hereditary, congenital disorders of skeletal growth can be mimicked in experimental animals by inducing nutritional deficiency of manganese. Manganese is required in the synthesis of mucopolysaccharides and in the glycosylation of collagen prior to its secretion. The similarity of lesions in experimental manganese deficiency and in congenital chondrodystrophies suggests the involvement of manganese-requiring enzymes in the hereditary disorder. Histological and histochemical studies in several laboratories have indicated defective matrix formation both in the experimental and the congenital condition. The nature of these defects is not understood. In the present studies, we propose to examine the role of several manganese- requiring enzymes in the orderly elaboration and deposition of connective tissue macromolecules. Our earlier studies indicated that glycosylation may be a necessary prerequisite for the secretion of collagen and since manganese is involved in this process, we also propose to examine if defective matrix may involve disturbances in the secretion of collagen.